DESCRIPTION: (Adapted from the author's abstract.) The reported incidence of pre- and perinatal transmission of HIV from an infected mother to the infant ranges from 30% to 50%. Although some evidence indicates that transplacental transfer of HIV can occur early in gestation, the precise mechanism by which maternal HIV transits the placenta is not known. The human placental "barrier," a fetally-derived organ which is the interface between maternal and fetal vascular systems, has been shown to be permeable to both cellular and soluble maternal elements. Transplacental transfer of HIV almost certainly occurs at the maternal-fetal vascular interface, where maternal blood bathes the fetal placental tissues. The placental cells that compose the lobular fetal cotyledons are themselves susceptible to HIV infection by virtue of both their location at the maternal-fetal interface and by their cell surface properties. Further, trophoblastic cells express Fc receptors for immunoglobulin and surface CD4. Fc receptors, functioning in transplacental transport of maternal immunoglobulin to the fetus, could also mediate transfer of HIV complexed with maternal anti-HlV IgG, or result in the enhancement of HIV infection of placental cells bearing Fc receptors. Certain observations should be noted: (a) the presence of HIV antigen in Fc receptor-bearing, CD4-positive Hofbauer cells has been demonstrated in the placenta in an HIV-positive pregnancy; (b) growth in different cell types has been shown to alter HIV tropism, thus influencing viral cytopathogenicity; (c) the effect of HIV passage through placental cells is not known but it may influence HIV tropism for fetal cell sub-populations; (d) infants infected in utero have a high incidence of multi-organ-system involvement as well as of immunologic dysfunction; and (e) the isolated perfused human placental cotyledon (IPC) has been used as a model to study transplacental transfer of soluble metabolites and drugs since 1967 and was used recently to evaluate transplacental transfer of zidovudine (AZT). Accordingly, the Principal Investigator proposes to use the IPC in novel investigations in order to delineate transplacental passage of HIV, immunoglobulins, and HIV:anti-HIV IgG complexes. She and her research associates will: (1) determine the efficiency of transplacental transfer of free virions and HIV-infected autologous maternal leukocytes in order and will quantify infected cells in the fetal circulation; (2) determine directly the relative efficiency of the transplacental passage of immunoglobulin of defined class and subclass, from the maternal circulation to the fetal circulation; and (3) localize the deposition of HIV:anti-HIV IgG complexes in the perfused placental lobule and investigate the potential enhancement of placental monocyte infection by HIV:IgG complexes, monitoring thereby immune complex-induced placental pathology.